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(Cancidas; L 743872; L 743873; MK 0991 )
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Caspofungin (Cancidas; L 743872; L 743873; MK 0991) is an antifungal drug. The first of a new class termed the echinocandins from Merck & Co., Inc. Caspofungin (Cancidas; L 743872; L 743873; MK 0991) shows activity against infections with Aspergillus and Candida, and works by inhibiting the enzyme β(1,3)-D-Glucan synthase and thereby disturbing the integrity of the fungal cell wall. Caspofungin (Cancidas; L 743872; L 743873; MK 0991) is administered intravenously.
1 . Condie CK, Tyler LS, Barker B, Canann DM. Visual compatibility of caspofungin acetate with commonly used drugs during simulated Y-site delivery. Am J Health Syst Pharm. 2008 Mar 1;65(5):454-7.
PURPOSE: The physical compatibility of i.v. caspofungin with other commonly used i.v. medications was tested.METHODS: Two methods were used to combine caspofungin and the secondary drugs. For drugs administered by i.v. push, caspofungin was delivered through a poly-vinyl chloride (PVC) i.v. solution set with secondary drugs injected into the Y-site of the i.v. extension set. For drugs given by i.v. infusion (over 10 minutes), secondary drugs were infused into the Y-site of the i.v. solution set through microbore PVC tubing. The two drugs shared 39 in of tubing. Attached to each end of the i.v. extension set were 0.8-mum filter disks. All drug combinations were tested three times; after each infusion, the filters were bubble-point tested. Drug combinations were considered physically compatible if no visible precipitate was seen and no color change was noted by the unaided eye during the infusion, or if the number of particles found on the filter under a microscope did not exceed the number stated in United States Pharmacopeia guidelines for particulate levels of large-volume parenteral fluids.RESULTS: A total of 8 of the 31 drugs tested (acyclovir, ceftriaxone, cefazolin, clindamycin, furosemide, heparin, pantoprazole, and piperacillin-tazobactam) were found to be physically incompatible with caspofungin.CONCLUSION: Caspofungin acetate was physically compatible during Y-site injection with 23 of 31 medications tested.
2 . Christopeit M, Eikam M, Behre G. Comedication of caspofungin acetate and cyclosporine A after allogeneic haematopoietic stem cell transplantation leads to negligible hepatotoxicity. Mycoses. 2008;51 Suppl 1:19-24.
Infections and adverse drug reactions both contribute substantially to mortality after allogeneic stem cell transplantation. It is therefore crucial to the transplant physician to develop an optimal anti-infective strategy, i.e. one which is highly effective and shows few side effects. Caspofungin acetate, the founding member of the echinocandins, is widely used against invasive fungal infections. We retrospectively assessed the hepatotoxicity of caspofungin acetate when administered with cyclosporine A. We reviewed the medical charts of 20 recipients of an allogeneic transplant. In detail, the median value of alanine amino transferase before, during and after administration of caspofungin acetate was 0.39 [standard error of the mean (SEM) 0.65], 0.77 (17) and 0.56 (0.77) micromol l(-1). The maximal value was 4-, 104- and 3.3-fold the upper normal level. The median value of aspartate amino transferase was 0.28 (SEM 0.45), 0.71 (26.26) and 0.60 (0.84) micromol l(-1). The maximal value before, during and after the administration of caspofungin acetate was 3.6-, 203- and 5.3-fold the upper normal level. The median value of gamma glutamyl transferase before, during and after administration of caspofungin acetate was 1.27 (SEM 1.78), 2.33 (3.41) and 1.77 (4.32) micromol l(-1). The maximal value was 1.38-, 2.53- and 1.93-fold the upper normal level. The median value of alkaline phosphatase before, during and after administration of caspofungin acetate was 1.11 (SEM 0.4), 1.97 (2.30) and 1.66 (5.48) micromol l(-1). The maximal value was 0.88-, 4.2- and 8.42-fold the upper normal level, respectively. The median value of total bilirubin before, during and after administration of caspofungin acetate was 23 (SEM 19.69), 38 (55.41) and 20 (67.23) micromol l(-1). The maximal value was 4.18-, 14.18- and 17.88-fold the upper normal level. Taken together, the elevations observed fell after the discontinuation of caspofungin acetate. This report is in accordance with published data. As expected, we did not find any evidence pointing to an increase in nephrotoxicity by caspofungin acetate.
3 . Rodriguez-Tudela JL, Gomez-Lopez A, Arendrup MC, Garcia-Effron G, Perlin DS, Lass-Fl?rl C, Cuenca-Estrella M. Comparison of caspofungin MICs by means of EUCAST method EDef 7.1 using two different concentrations of glucose. Antimicrob Agents Chemother. 2010 Jul;54(7):3056-7.
According to the product insert for Cancidas (caspofungin acetate), the drug must not be diluted in solutions containing glucose as this decreases caspofungin stability. The aim of this study was to compare caspofungin MICs for a collection of yeasts by means of EUCAST method EDef7.1 but using two different concentrations of glucose: 2% versus 0.2%. MICs were identical or within one 2-fold dilution for 93 out of 95 strains (97.9%), showing that glucose does not interfere with susceptibility.
4 . Mojumder DK, Concepcion FA, Patel SK, Barkmeier AJ, Carvounis PE, Wilson JH, Holz ER, Wensel TG. Evaluating retinal toxicity of intravitreal caspofungin in the mouse eye. Invest Ophthalmol Vis Sci. 2010 Nov;51(11):5796-803.
PURPOSE: Caspofungin is a synthetic echinocandin antifungal agent that inhibits the synthesis of β(1,3)-D-glucan, an essential component of the cell wall of susceptible Aspergillus and Candida species. In this study, retinal toxicity was determined after intravitreal injection of caspofungin in a mouse model to assess its safety profile for the treatment of fungal endophthalmitis.METHODS: Caspofungin acetate was injected intravitreally in the left eyes of male C57BL/6 mice, with final vitreal concentrations corresponding to 0.41, 1.2, 2.5, 4.1, and 41 μM (five mice per cohort). A total of 25 age-matched male C57BL/6 mice injected with balanced salt solution were used as control subjects (five for each of the five different caspofungin acetate concentrations). Electroretinograms (ERGs) were recorded 7 weeks after the injections, and the injected eyes were examined histologically.RESULTS: Mice injected with caspofungin at vitreal concentrations from 0.41 to 4.1 μM did not have significant alterations in their ERG waveforms, and their retinas had no detectable morphologic changes or loss of cells. At the vitreal concentration of 41 μM, caspofungin reduced the amplitudes of the a-waves, b-waves, and scotopic threshold responses of the ERG and also produced a decrease in the number of cells in the ganglion cell layer.CONCLUSIONS: Caspofungin is a safe antifungal agent at vitreal concentrations of 0.41 to 4.1 μM in mice and consequently shows promise for the treatment of fungal endophthalmitis in humans. Much higher doses produce toxicity and should not be used.
5 . Flattery, Amy M. et al. Efficacy of caspofungin in a juvenile mouse model of central nervous system candidiasis Antimicrobial Agents and Chemotherapy (2011), 55(7), 3491-3497.
Neonatal candidiasis is an increasingly common occurrence causing significant morbidity and mortality and a higher risk of dissemination to the central nervous system (CNS) than that seen with older patients. The current understanding of optimal antifungal therapy in this setting is limited. We have developed a model of disseminated candidiasis with CNS involvement in juvenile mice to assess the efficacy of the echinocandin caspofungin relative to amphotericin B (AmB). Juvenile mice were inoculated intravenously with 5.64 × 104 CFU of Candida albicans MY1055. Treatment with caspofungin at 1, 2, 4, and 8 mg/kg of body weight/day, AmB at 1 mg/kg/day, or a vehicle control (VC) was initiated 30 h after infection and continued for 7 days. Pharmacokinetic parameters for caspofungin were also determined. ...
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